Recent investigations have shown that malignant transformation may down-regulate the expression of class I HLA molecules, beta2-microglobulin (beta2m) and members of the antigen-processing machinery. In the present study, we HLA-genotyped and identified at a biochemical level the three (HLA-A25, -B8, -Cw7) class I alleles expressed by the previously described [D'
Urso CM et al (1992) J Clin Invest 87: 284-292] beta2m-defective human
melanoma FO-1 cell line and tested their ability to interact with
calnexin,
calreticulin and the
TAP (transporter associated with antigen processing) complex. All these alleles were found to bind
calnexin, but not
calreticulin or the poorly expressed TAP complex, both in parental and beta2m-transfected FO-1 cells, demonstrating a complex defect of class I expression in FO-1 cells. In these conditions, Cw7 heavy chains interacted with
calnexin more strongly than A25 and B8, and preferentially accumulated in the endoplasmic reticulum, in both a
calnexin-associated and a
calnexin-free form. In addition, they could be transported to the cell surface at low levels even in the absence of beta2m, without undergoing terminal glycosylation. These results establish a parallel between
HLA-C and the murine Db and Ld molecules which have been found to be surface expressed and functional in beta2m-defective cells. They also demonstrate distinctive features of
HLA-C molecules. We propose that the accumulation of several assembly intermediates of
HLA-C might favour the binding of
peptide antigens not readily bound by
HLA-A and -B molecules in neoplastic cells with suboptimal class I expression.